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Series GSE123339 Query DataSets for GSE123339
Status Public on May 02, 2023
Title Oncogenic CDK13 Mutations Impede Nuclear RNA Surveillance (mouseRNAseq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We find disrupted nuclear RNA surveillance is oncogenic. Cyclin Dependent Kinase 13 (CDK13) is mutated in melanoma and patient-mutated CDK13 accelerates zebrafish melanoma. CDK13 mutation causes aberrant RNA stabilization. CDK13 is required for ZC3H14 phosphorylation, which is necessary and sufficient to promote nuclear RNA degradation. Mutant CDK13 fails to activate nuclear RNA surveillance, causing aberrant protein-coding transcripts to be stabilized and translated. Forced aberrant RNA expression accelerates melanoma in zebrafish. We find recurrent mutations in genes encoding nuclear RNA surveillance components in many malignancies, establishing nuclear RNA surveillance as a tumor-suppressive pathway. Activating nuclear RNA surveillance is crucial to avoid accumulation of aberrant RNAs and their ensuing consequences in development and disease.
Overall design V6.5 mouse embryonic stem cells with endogenous Cdk13 knock out complemented by doxycycline (Dox)-inducible Flag- HA- epitope tagged Cdk13 transgene (Cdk13△) were grown in the presence of Cdk13 (+Dox) or were depleted of Cdk13 (-Dox). RNA sequencing experimental design: PolyA-selected RNA was isolated from two independently derived Cdk13△ clones each in biological duplicate for cells maintained in Dox (+Dox), withdrawn from Dox for 48 hours (-Dox 48hrs), or withdrawn from Dox for 72 hours (-Dox 72hrs). A total of 12 libraries were prepared and sequenced.
Contributor(s) Dubbury SJ, Boutz PL, Sharp PA
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Submission date Dec 04, 2018
Last update date May 02, 2023
Contact name Sara Jane Dubbury
Phone 425-501-0761
Organization name MIT
Department Koch Institute
Lab Phillip Sharp
Street address 500 Main Street, 76-417
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM3501183 Cdk13Δ_c11-8_plusDox_rep1
GSM3501184 Cdk13Δ_c11-8_plusDox_rep2
GSM3501185 Cdk13Δ_c14-1_plusDox_rep1
This SubSeries is part of SuperSeries:
GSE131334 Oncogenic CDK13 Mutations Impede Nuclear RNA Surveillance
BioProject PRJNA508379
SRA SRP172489

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Supplementary file Size Download File type/resource
GSE123339_Cdk13_48_72_All_DEXSeq_results.xlsx 13.0 Mb (ftp)(http) XLSX
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